The TRPV4 ion channel in skin keratinocytes has a significant role to play in the formation and maintenance of barrier function to offset dehydration, a new research has revealed.
Japanese research group led by Prof. Makoto Tominaga and Dr. akaaki Sokabe (National Institute for Physiological Sciences: IPS) found that TRPV4, one of the temperature-sensitive Ca2+-permeable channels, namely "thermoTRPs", acts as a warm sensor to choose preferred environmental temperatures in mammals.
The research group sought the alternative function of TRPV4, since skin keratinocytes express another thermoTRP named TRPV3, which also functions as a warm sensor.
TRPV4 was found to interact with b-catenin, an adaptor protein between actin filaments and E-cadherin in cell-cell junction complex. When TRPV4 was genetically removed from keratinocytes, Ca2+-induced cell-cell junction formation was delayed and immature, resulting in leaky junctions.
Consistently, intercellular junction-dependent skin barrier in TRPV4-deficient mice became weak (leaky intercellular pathway) compared to wild-type mice. Interestingly, these phenotypes were TRPV4-specific, but not TRPV3-dependent.
Dr. Sokabe said, "TRPV4 may utilize skin temperature to provide Ca2+ for cell-cell junction complexes to reinforce their tightness. For instance, dried skin in cold seasons or regions could be due to low activity of TRPV4 caused by low skin temperature. Development of chemicals modulating TRPV4 activity would be useful for barrier repair of damaged skin."